Diagnostic accuracy, clinical utility and influence on decision making of a methylation urine biomarker test in the surveillance of non-muscle-invasive bladder cancer.

To prospectively investigate the clinical utility and influence on decision making of Bladder EpiCheckTM , a non-invasive urine test, in the surveillance of non-muscle-invasive bladder cancer (NMIBC).

Urine samples from 440 patients undergoing surveillance for NMIBC were prospectively collected at five centers and evaluated using the Bladder EpiCheckTM test (NCT02647112). Multivariable nomogram and decision curve analysis (DCA) were used to evaluate the impact of Bladder EpiCheck TM on decision making when used in clinical routine. The test was designed to rule out recurrent disease.

Data from 357 patients was available for analysis. The test had a specificity of 88% (95% CI 84 - 91) and a negative predictive value (NPV) of 94.4% (95% CI 91 - 97) for the detection of any cancer and a NPV of 99.3% for the detection of high grade cancer. In multivariable analysis, positive Bladder EpiCheck TM results were independently associated with any and high-grade disease recurrence (OR 18.1; 95%CI 8.7 - 40.2; p < 0.001 and OR 78.3; 95%CI 19.2 - 547; p < 0.001). Addition of Bladder EpiCheck TM to standard variables improved its prediction for any and high-grade disease recurrence by a difference of 16% and 22%, respectively (area under the curve 85.9% and 96.1% for any and high-grade cancer). DCA showed an improvement in the net benefit relative to cystoscopy over a large threshold of probability, resulting in a significant reduction of unnecessary investigations. These results were similar in subgroups assessing the impact of specific clinical features.

Bladder EpiCheckTM is a robust high performing diagnostic test in patients with NMIBC undergoing surveillance, potentially reducing the number of unnecessary investigations. This article is protected by copyright. All rights reserved.

BJU international. 2019 Jan 17 [Epub ahead of print]

David D'Andrea, Francesco Soria, Sonja Zehetmayer, Kilian M Gust, Stephan Korn, J Alfred Witjes, Shahrokh F Shariat

Department of Urology, Medical University of Vienna, Vienna, Austria., Center for Medical Statistics, Informatics, and Intelligent Systems, Medical University of Vienna, Vienna, Austria., Department of Urology, Radboud University Nijmegen Medical Center, Nijmegen the Netherlands.